RIMKLA (ribosomal modification protein rimK like family member A) is a cytoplasmic ATP-grasp ligase that catalyzes synthesis of N-acetyl-L-aspartyl-L-glutamate (NAAG) and N-acetylaspartylglutamylglutamate (NAAG₂) 12. The enzyme is predominantly expressed in the central nervous system, where NAAG functions as a group II metabotropic glutamate receptor agonist 2. Beyond its canonical neuropeptide role, RIMKLA exhibits novel protein kinase activity that phosphorylates betaine-homocysteine S-methyltransferase 1 (BHMT1) at threonine 45, activating homocysteine metabolism and suppressing hepatic lipid synthesis and uptake 3. In metabolic disease, RIMKLA expression is reduced in nonalcoholic fatty liver disease (NAFLD), and hepatic RIMKLA overexpression ameliorates steatosis and hyperglycemia in obese mice through BHMT1-mediated repression of fatty acid synthase and CD36 gene transcription 3. RIMKLA has been identified as a differentially expressed glutamine metabolism-related gene in diabetic foot ulcer and thyroid carcinoma pathogenesis 45, and is upregulated under hypoxic conditions in triple-negative breast cancer 6. While candidate disease-causing variants in RIMKLA have been identified 7, its precise therapeutic potential in metabolic and neoplastic diseases requires further investigation.