StAR-related lipid transfer domain containing 9 (STARD9)

STARD9 (StAR-related lipid transfer domain containing 9) is a large kinesin motor protein (∼517 kDa) that uniquely combines an N-terminal kinesin motor domain with a C-terminal START lipid transfer domain[1][3]. It plays critical roles in both mitosis—regulating pericentriolar material cohesion for bipolar spindle assembly—and in lysosome-endosome (LE/L) membrane motility and tubulation, particularly in neurons and other cells. STARD9 is phosphorylated during mitosis by kinases such as Plk1 and is targeted for ubiquitin-proteasome degradation, thereby tightly regulating its cellular levels for proper cell division[1]. Disruption of STARD9 function leads to spindle assembly defects, mitotic arrest, reduced cell viability, and cholesterol accumulation within lysosomes, mimicking features seen in NPC1 mutations[3]. Its molecular features include a kinesin motor domain with a unique regulatory insertion, a membrane association signal similar to lysosomal membrane proteins, and N-linked glycosylation, indicating synthesis through the secretory pathway[1][3]. Although not yet a clinical drug target, STARD9 remains a candidate for cancer therapy due to its essential role in mitotic progression[1][3].

Other names

StAR-related lipid transfer protein 9START domain-containing protein 9KIAA1300KIF16A (note: KIF16A may be an incorrect alias; STARD9 shows higher homology to KIF16B than KIF16A, and may not correctly correspond to KIF16A[3])StARD9

Not established for clinical drugs. Experimental approaches (e.g., shRNA-mediated gene silencing) disrupt mitotic spindle formation, lysosome motility, and cholesterol trafficking[3].