The function of ORMDL2 (ORMDL sphingolipid biosynthesis regulator 2, Ensembl gene identifier ENSG00000123353) is as follows. Plays an essential role in the homeostatic regulation of sphingolipid de novo biosynthesis by modulating the activity of the serine palmitoyltransferase (SPT) in response to ceramide levels (PubMed:20182505). When complexed to SPT, the binding of ceramides to its N-terminus stabilizes a conformation that block SPT substrate entry, hence preventing SPT catalytic activity. Through this mechanism, maintains ceramide levels at sufficient concentrations for the production of complex sphingolipids, but which prevents the accumulation of ceramides to levels that trigger apoptosis (By similarity). {ECO:0000250|UniProtKB:Q8N138, ECO:0000269|PubMed:20182505}.