GCSH (glycine cleavage system protein H) is a mitochondrial protein with dual metabolic functions. Functionally, GCSH serves as the lipoyl carrier protein (H-protein) in the glycine cleavage system, shuttling the methylamine group from the P-protein to the T-protein during glycine degradation 1. Beyond glycine metabolism, GCSH has a pivotal moonlighting role in protein lipoylation, facilitating the lipoylation of critical bioenergetic enzymes including pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase 1. This lipoylation function is promoted by direct binding of the lipoyl synthase (LIAS) enzyme to GCSH, a process regulated upstream by ferredoxin FDX1 2. Disease relevance is significant: biallelic GCSH variants cause combined nonketotic hyperglycinemia and lipoate deficiency, with clinical manifestations ranging from neonatal fatal glycine encephalopathy to attenuated developmental delay and seizures 1. Heterozygous mutations may cause transient neonatal hyperglycinemia 3. GCSH dysregulation is also implicated in cancer progression; elevated GCSH expression in endometrial cancer correlates with poor prognosis, immune suppression, and therapeutic resistance 4. GCSH is differentially expressed across metabolic dysfunction-associated fatty liver disease stages 5 and serves as a prognostic biomarker in acute myeloid leukemia 6. GCSH expression is ubiquitous across tissues 7, highlighting its broad metabolic importance.