ATPSCKMT (ATP synthase c subunit lysine N-methyltransferase, also known as FAM173B) is a mitochondrial protein-lysine N-methyltransferase that catalyzes trimethylation of lysine-43 on ATP synthase subunit C (ATP5MC1 and ATP5MC2) 1. This post-translational modification is essential for proper incorporation of the C subunit into the ATP synthase complex and optimal ATP generation 1. Cells lacking ATPSCKMT show aberrant ATP synthase assembly, decreased ATP-generating capacity, and reduced mitochondrial respiration 1. Beyond bioenergetic functions, ATPSCKMT plays a critical role in chr5 pain pathophysiology. Its methyltransferase activity in sensory neuron mitochondria promotes both inflammatory and neuropathic pain through reactive oxygen species (ROS)-dependent mechanisms and microglial activation 2. Recent evidence indicates that inflammation-induced upregulation of ATPSCKMT causes mitochondrial dysfunction in sensory neurons, leading to impaired resolution of acute inflammatory pain and predisposing to chr5 pain development 3. Inhibition of ATPSCKMT or supplementation of affected metabolites restores normal pain resolution and prevents chr5 pain 3. Clinically, ATPSCKMT expression associates with inflammatory knee osteoarthritis, where altered expression correlates with inflammatory mediator levels and pain sensitivity 4. These findings identify ATPSCKMT as a potential therapeutic target for chr5 pain conditions.