An unprecedented international effort to decode how cells manage the transport of chemical substances has culminated in four groundbreaking studies published in *Molecular Systems Biology*. Led by Giulio Superti-Furga at CeMM, the Research Centre for Molecular Medicine of the Austrian Academy of Sciences, and supported by an international consortium of academic and pharmaceutical partners under the European Union's Innovative Medicines Initiative, this decade-long project provides the first comprehensive functional blueprint of chemical transport pathways in human cells.

All life depends on the ability of cells to exchange substances with their environment. Nutrients, ions, and vitamins must be absorbed, while waste and special metabolites must be expelled. This fundamental process relies on transporter proteins embedded in cell membranes. Despite their crucial role, the function of many of the hundreds of human transporter-encoding genes has remained a mystery, slowing progress in fields ranging from cancer therapy to metabolic and neurological disease research.

Recognising this challenge, the Superti-Furga group at CeMM first called for intensified research in a landmark 2015 article in *Cell*. Ten years later, CeMM and an international consortium have succeeded: by focusing on the largest family of transporters—the solute carriers (SLCs)—they have more than doubled existing knowledge and laid the foundations for future breakthroughs in understanding and targeting these critical proteins.

A megaproject on membrane transporters

In a massive, coordinated effort, 120 researchers from 13 institutions across eight countries came together under the RESOLUTE consortium. After more than five years of laboratory work, most of the experimental data had been gathered. The CeMM team, supported by a few key partners and primarily financed by the Austrian Academy of Sciences, then spent an additional year harmonising, integrating, and interpreting the extensive datasets.

The result is a transformative expansion of the known biology of SLC transporters, integrating multidisciplinary experimental and computational approaches. Their findings illuminate the intricate logistics of chemical traffic within human cells, offering powerful new resources for the scientific and medical communities worldwide. "It is difficult to find in history a comparably ample and strong 'push' of enabling knowledge and tools towards an individual target class, so heavily involved in human disease," says Giulio Superti-Furga, scientific director of CeMM and coordinator of the RESOLUTE consortium. "With these four studies, we hope to have lowered the barrier for transporter research and catalysed a surge in biomedical discovery for years to come."

The effort not only generated vast scientific insights but also produced an impressive arsenal of reagents, datasets, and analytical tools—all made freely available to the global scientific community via https://re-solute.eu. "What is the most important outcome is that we were able to annotate most, if not all, solute carriers with functional information and have created a vast arsenal of tools that now serve the global research community. This achievement, culminating in the RESOLUTE knowledge base, represents a unique resource and a true community treasure," says Ulrich Goldmann, a key researcher responsible for data integration.

Giulio Superti-Furga adds: "We are deeply grateful for the support of the Innovative Health Initiative, IHI (previously the Innovative Medicines Initiative, IMI), a partnership of the European Federation of Pharmaceutical Industries and Associations, EFPIA, and the European Union, EU, and the contributions of all our outstanding partners—without whom this project would never have come to life. For a couple of years, CeMM has shouldered much of the responsibility to validate, annotate, maintain, and further develop this invaluable platform.

Looking ahead, there is a genuine opportunity for funding bodies and industry stakeholders to help secure the long-term sustainability and expansion of this effort. It is not too late to propose and contribute the means to ensure this community treasure continues to grow and inspire biomedical research worldwide." Project manager Tabea Wiedmer, WHO, took over after the premature and tragic death of Daniel Lackner, emphasises the collaborative spirit of the initiative: "Coordinating the research efforts of such a large group of scientists was a formidable challenge, especially during COVID. We had to develop all sorts of creative strategies to keep partners focused and motivated, but it worked wonderfully. The success relies heavily on efficiently combining expertise across fields."

Key highlights of the four landmark studies

Unlocking new therapeutic opportunities

SLC transporters are implicated in a wide range of diseases, including cancer, neurological disorders, diabetes, and inherited metabolic conditions. Furthermore, the efficacy of numerous drugs depends on their ability to traverse cellular membranes via specific transporters. By dramatically expanding the knowledge on transporters and providing essential tools, RESOLUTE paves the way for accelerated therapeutic innovation and new precision medicine approaches.