SorCS1, also known as sortilin-related Vps10p (vacuolar protein sorting/targeting protein 10) domain-containing receptor 1, is a protein sorting receptor. It is crucial for the trafficking of neuronal receptors and participates in multiple biological pathways, such as those related to synaptic function, metabolism, and renal function. Genetic models, like knockout mouse models, have been valuable in studying its functions [1,2,3,4,5].

In synaptic function, SorCS1 competes with amyloid-β oligomers (AβOs) for β-neurexin (NRX) binding, rescuing AβO-induced synaptic pathology [1]. It also maintains the axonal-dendritic balance of NRX surface levels, ensuring proper presynaptic differentiation and function [2].

In metabolism, SorCS1, along with SORCS3, controls energy balance and orexigenic peptide production in the hypothalamus [3].

In renal function, Sorcs1 affects protein trafficking in the kidney, and its genetic variation is associated with renal disease in rats and humans [4].

In β-cells, Sorcs1 is necessary for normal insulin secretory granule biogenesis under metabolic stress [5].

In conclusion, SorCS1 plays essential roles in synaptic function, metabolism, renal function, and insulin secretion. Studies using KO mouse models have significantly contributed to understanding its functions in diseases like Alzheimer's disease, metabolic disorders, and renal diseases.