SPTLC1 Recombinant Rabbit mAb (S-6028)

SPTLC1 (serine palmitoyltransferase long chain base subunit 1) is one of the catalytic core subunits of serine palmitoyltransferase (SPT) encoded by the SPTLC1 gene. This enzyme is the key rate-limiting enzyme in the de novo sphingolipid biosynthesis pathway, catalyzing the condensation of L-serine and palmitoyl-CoA to generate 3-ketodihydrosphingosine on the endoplasmic reticulum membrane, providing essential precursors for the synthesis of all sphingolipids (such as ceramides and sphingomyelins). This protein belongs to the type II pyridoxal phosphate-dependent aminotransferase family, possessing an N-terminal transmembrane domain that anchors it to the endoplasmic reticulum membrane, while the majority of its C-terminal domain resides in the cytoplasm to perform catalytic functions. SPTLC1 must form heterodimers with SPTLC2 or SPTLC3, and then assemble with auxiliary subunits SPTSSA or SPTSSB to form the complete SPT complex, with its substrate preference varying depending on the complex composition; meanwhile, its activity is tightly regulated by negative feedback from the ORMDL protein family to maintain sphingolipid homeostasis. Dysfunction of SPTLC1 is closely associated with various diseases: specific mutations in SPTLC1 alter the enzyme's substrate selectivity, leading to the abnormal synthesis of neurotoxic deoxysphingolipids, which causes autosomal dominant hereditary sensory and autonomic neuropathy type 1A (HSAN1A); while another class of mutations located in the N-terminal transmembrane domain (such as A20T) disrupts ORMDL-mediated inhibition, resulting in excessive SPT activity and accumulation of canonical sphingolipids, which is associated with juvenile amyotrophic lateral sclerosis (ALS27); additionally, SPTLC1 expression is significantly reduced in clear cell renal cell carcinoma, and its overexpression can exert tumor-suppressive effects by inhibiting the EGFR/VEGFR signaling pathway and epithelial-mesenchymal transition, with low expression predicting poor patient prognosis.