Serine palmitoyltransferase, long chain base subunit 2 (SPTLC2)

Serine palmitoyltransferase, long chain base subunit 2 (SPTLC2) is the catalytic subunit of the serine palmitoyltransferase (SPT) complex, which catalyzes the initial and rate-limiting step in sphingolipid biosynthesis—the condensation of L-serine with palmitoyl-CoA to generate long-chain base precursors[1][4]. The SPT complex consists of SPTLC1 (structural/supporting subunit), SPTLC2 (catalytic subunit), and small regulatory subunits (ssSPTa/ssSPTb) that determine substrate specificity; together, this complex controls cellular sphingolipid production[1][2][3]. SPTLC2 requires the pyridoxal-5′-phosphate (PLP) cofactor for activity, with unique substrate selectivity properties conferred by regulatory module interactions[1]. Dysregulation of SPTLC2 activity, via mutations or altered expression, impacts ceramide synthesis—a critical event in metabolic homeostasis, cell signaling, and membrane structure. Elevated SPTLC2 function is associated with ER stress-induced ceramide accumulation, insulin resistance, and neurotoxicity, while its inhibition (e.g., by myriocin) has implications for reducing sphingolipid-linked pathology[5]. SPTLC2 is a validated molecular therapeutic target in metabolic disorders, neuropathies, and inflammatory disease research[1][5].

Other names

SPTLC2KIAA0526LCB2LCB2ahLCB2aSPT2Long chain base biosynthesis protein 2Long chain base biosynthesis protein 2aSerine-palmitoyl-CoA transferase 2HSN1CNSAN1CSPT 2serine palmitoyltransferase 2serine-palmitoyl-CoA transferase 2

Competitive inhibition of substrate binding (e.g., myriocin reacts with the PLP cofactor at SPTLC2’s active site, mimicking substrate and blocking enzymatic activity)