tip47

TIP47, also known as perilipin-3 (PLIN3), is a 47-kilodalton cytosolic protein that associates with lipid droplets and with late endosome compartments. It is a member of the perilipin family of lipid droplet–associated proteins and is encoded by the PLIN3 gene in humans. TIP47 was identified as a Rab9 effector that links Rab9 GTPase to endosome-to-Golgi transport, and it is involved in intracellular trafficking rather than being a constitutive structural component of the lysosome itself.

In its active, GTP-bound state, Rab9 binds TIP47 on late endosomes, and TIP47 participates in the retrograde transport of the mannose-6-phosphate receptor (CI-MPR) from late endosomes to the trans-Golgi network. This transport step is important for the proper sorting and delivery of lysosomal hydrolases. By facilitating receptor recycling, TIP47 contributes to lysosome biogenesis and enzyme targeting within the cell.

Localization and interactions of TIP47 are dynamic. It localizes to late endosomes and the trans-Golgi network in a Rab9-dependent manner, and it can also associate with lipid droplets under certain cellular conditions, such as during adipocyte differentiation or changes in lipid metabolism. The protein contains features characteristic of the PAT domain family found in perilipins, along with regions that mediate Rab9 interaction and subcellular targeting.

Functionally, TIP47 links endosomal trafficking to lysosome biogenesis and may intersect with lipid droplet biology. Its activity highlights the interconnected nature of intracellular transport pathways and lipid metabolism.