Finding functional microproteins

Genome-wide translational profiling has uncovered the synthesis in human cells of thousands of microproteins, a class of proteins traditionally overlooked in functional studies. Although an increasing number of these microproteins have been found to play critical roles in cellular processes, the functional relevance of the majority remains poorly understood. Studying these low-abundance, often unstable proteins is further complicated by the challenge of disentangling their functions from the noncoding roles of the associated DNA, RNA, and the act of translation. This review highlights recent advances in functional genomics that have led to the discovery of >1000 human microproteins required for optimal cell proliferation. Ongoing technological innovations will continue to clarify the roles and mechanisms of microproteins in both normal physiology and disease, potentially opening new avenues for therapeutic exploration.