Acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3B)

Acid sphingomyelinase-like phosphodiesterase 3b (SMPDL3B) is a membrane-associated lipid-modifying enzyme belonging to the phosphodiesterase family. It is attached to the plasma membrane via a GPI anchor and regulates sphingolipid metabolism and membrane fluidity, primarily in immune cells such as macrophages and dendritic cells, as well as in specialized kidney cells (podocytes). SMPDL3B functions as a negative regulator of innate immune response and Toll-like receptor signaling, influencing cell membrane lipid composition by modulating the levels of sphingomyelin, phosphatidylcholine, and ceramide. Its excess or deficiency has been implicated in kidney diseases like diabetic kidney disease and nephrotic syndrome; overexpression can protect cells from apoptosis, while reduction may aggravate cellular injury. SMPDL3B is notable for being an off-target of rituximab, which may contribute to its therapeutic effects in nephrotic syndrome. Despite its homology to acid sphingomyelinase and SMPDL3A, SMPDL3B has a unique substrate binding cavity and different substrate specificity; while it may target sphingomyelin and other phosphocholine headgroup lipids, its physiological substrates remain incompletely characterized

Other names

SMPDL3BAcid sphingomyelinase-like phosphodiesterase 3bASM-like phosphodiesterase 3bASML3BASMLPD

Rituximab: indirectly alters SMPDL3B’s function and expression in podocytes, correlating with clinical improvement in nephrotic syndrome