Leptin receptor overlapping transcript protein (LEPROT)

Leptin receptor overlapping transcript protein (LEPROT, also called endospanin-1) is a highly conserved small transmembrane protein associated with the Golgi complex and endosomes.[1][3] Its primary function is to regulate cell surface expression—and therefore signaling activity—of several hormone receptors, most notably the **leptin receptor (LEPR)** and **growth hormone receptor (GHR)**.[1][3] LEPROT acts as a negative modulator, restricting the number of these receptors available at the cell surface, which dampens downstream signaling responses to leptin and growth hormone. In the brain, LEPROT impairs leptin receptor trafficking in hypothalamic neurons and thereby contributes to **leptin resistance**, a key factor in the development of obesity.[1] LEPROT is implicated in the regulation of insulin signaling, growth, and metabolic traits. Aberrant expression of LEPROT has been observed in multiple cancers, where it is associated with immune and inflammatory signaling pathways (notably IL-6/JAK/STAT), and can serve as a prognostic marker in certain tumor types.[4] Genome-wide associations and epigenetic studies link LEPROT regulation to metabolic outcomes, such as BMI and diabetes risk.[1][4] No drugs are currently known to selectively target LEPROT, and it is not a classical receptor, enzyme, or transporter, but a regulatory protein acting primarily on hormone receptor trafficking and signaling.[1][3][4]

Other names

OB-R gene-related proteinendospanin-1leptin receptor gene-related proteinOBRGRPOB-RGRPVPS55LEPRFLJ90360endospaninLeptin receptor overlapping transcriptOBRGO15243

Not established for direct targeting; indirect functional impact via modulation of cell surface presentation and signaling of receptors (especially leptin and growth hormone receptors)