SorCS1, also known as sortilin-related Vps10p (vacuolar protein sorting/targeting protein 10) domain-containing receptor 1, is a protein sorting receptor. It plays crucial roles in multiple biological processes such as synaptic function, metabolism regulation, and protein trafficking. It is involved in pathways related to axonal trafficking of neurexins and endosomal sorting, and is of great biological importance in maintaining normal physiological functions [1].

In mouse models, whole-body Sorcs1 KO mice with the leptin(ob) mutation developed diabetes, indicating Sorcs1 is necessary for normal insulin secretory granule biogenesis in metabolically stressed β cells [4]. Also, SORCS1 and SORCS3 double-deficient mutant mice showed excessive production of orexigenic neuropeptide, enhanced food intake, and increased adiposity, suggesting SORCS1 controls energy balance [2]. In addition, SorCS1 knockout in a rat strain with a sensitized genome background led to increased proteinuria, showing its role in maintaining proper renal function [3].

In conclusion, SorCS1 is essential for synaptic function, metabolism, and renal function as revealed through model-based research. Mouse and rat knockout models have significantly contributed to understanding its role in diabetes, energy balance regulation, and renal disease, providing insights into potential therapeutic strategies for these diseases.