SPAAR is a microprotein that negatively regulates amino acid sensing through inhibition of mTORC1, a signaling complex that promotes cell growth. It functions by promoting formation of a tightly bound supercomplex composed of the lysosomal V-ATPase, Ragulator, and Rag GTPases, which prevents mTORC1 recruitment to lysosomes upon amino acid stimulation [UniProt Function]. SPAAR also regulates muscle regeneration and angiogenesis through interactions with conserved signaling pathways 1. The protein is evolutionarily ancient, present in marsupials and monotremes, though it shows substantial sequence divergence across mammals and evidence of adaptive evolution in primates, particularly in recently evolved 5' elongated isoforms 1. SPAAR is produced from the LINC00961 locus, which also encodes a long non-coding RNA with opposing angiogenic effects; the transcript regulates endothelial cell adhesion, tube formation, migration, proliferation, and barrier integrity 2. Common variants in SPAAR associated with cardiovascular function have been detected through genome-wide analysis 3. Loss of the LINC00961/SPAAR locus in mice results in sex-specific developmental delays, altered cardiac dimensions, and increased risk area following myocardial infarction, suggesting the locus contributes to cardiac endothelial cell and fibroblast function 4.