Progestin and adipoQ receptor family member 4 (PAQR4)

Progestin and adipoQ receptor family member 4 (PAQR4) is a seven-transmembrane domain protein of the progestin and adipoQ receptor (PAQR) family, primarily localized to the Golgi apparatus rather than the plasma membrane[1][6][12]. PAQR4 regulates adipocyte function and metabolic health by controlling ceramide levels through the stabilization of ceramide synthases (CERS2 and CERS5), thereby influencing adipose tissue remodeling, adipogenesis, and whole-body glucose homeostasis[1][4][7][10][12]. Unlike PAQR1/AdipoR1 and PAQR2/AdipoR2, PAQR4 does not respond to adiponectin but is implicated in negative regulation of adipogenesis and promotion of macrophage infiltration and fat mass reduction when overexpressed or knocked out in adipocytes[1][4]. In cancer biology, PAQR4 is found upregulated in multiple tumor types, including breast, lung, gastric, prostate, and liver cancers, where its higher expression is associated with increased cell proliferation, chemoresistance (notably through stabilization of Nrf2 in NSCLC and inhibition of apoptotic pathways), and poor clinical outcome[2][5][6][8]. Although PAQR4 is considered a potential therapeutic target for metabolic syndrome and cancer, it is currently an orphan receptor with no clinically validated drugs directly targeting it[1][6]. PAQR4's dual roles in metabolic regulation and oncogenic processes make it a promising, yet challenging, candidate for future therapeutic development and as a prognostic biomarker in various diseases.

Other names

PAQR4FLJ30002Progestin and adipoQ receptor family member IVprogestin and adipoQ receptor family member 4

For hypothetical drugs, would include modulation of ceramide metabolism by interfering with PAQR4’s stabilization of ceramide synthases or inhibition of anti-apoptotic functions in cancer cells[1][2][7].