Solute carrier family 35 member D3 (SLC35D3)

Solute carrier family 35 member D3 (SLC35D3) is a UDP-glucose transmembrane transporter localized primarily to early endosomes and the endoplasmic reticulum in certain cells, including neurons and megakaryocytes. It plays several crucial physiological roles: - Dopaminergic signaling: In neurons, SLC35D3 regulates the trafficking of dopamine D1 receptor (DRD1) to the plasma membrane. Loss-of-function mutations cause D1 receptor retention in the ER, impair dopamine signaling, and result in obesity/metabolic syndrome, which can be rescued by D1 receptor agonists. - Platelet function: SLC35D3 is implicated in the formation and function of dense granules in platelets. Mutations lead to storage pool defects and associated bleeding disorders. - Metabolic regulation: It influences adipogenesis and the browning of white adipose tissue; its dysfunction is associated with metabolic syndrome and possibly cardiovascular disease. - Cancer: A growing body of evidence suggests that SLC35D3 is upregulated in certain cancers, such as colorectal and prostate cancer, and may promote tumor progression via AMPK signaling. SLC35D3 is thus a multifunctional transporter with emerging roles in metabolic regulation, platelet biology, and tumorigenesis, although it is not yet a direct pharmacological drug target.

Other names

FRCL1Fringe connection-like protein 1frcfringe-like 1

Not drug-targeted directly; however, SLC35D3 loss leads to impaired dopamine D1 receptor trafficking and signaling—thus, D1 receptor agonists can compensate for SLC35D3 dysfunction.