Slc66a1-flox Mouse

Slc66a1, also known as PQLC2, is a lysosomal cationic amino acid transporter [4,5,6,7]. It plays a crucial role in maintaining amino acid homeostasis and is involved in the autophagy-lysosome pathway [1]. It can act as a sensor, responding to cationic amino acid scarcity by recruiting a protein complex composed of C9orf72, SMCR8, and WDR41 to lysosome surfaces, thereby controlling multiple aspects of lysosome function [4].

Genetic studies have associated Slc66a1 with several diseases. Homozygous pathogenic variants in Slc66a1 have been found to cause autosomal recessive retinitis pigmentosa (ARRP) [2]. Analysis of genome sequencing data from rare-disease parent-child trios also identified Slc66a1 as a likely novel cause for autosomal recessive rod-cone dystrophy [3]. In addition, PQLC2 is overexpressed in gastric cancer tissues, especially of the diffuse type, and its overexpression promotes cancer cell growth, suggesting it could be a potential therapeutic target in gastric cancer [6].

In conclusion, Slc66a1 is essential for lysosomal cationic amino acid transport and lysosome-related functions. Its role in autosomal recessive retinopathies and potential as a cancer therapeutic target, as revealed through genetic and disease-associated studies, highlight its significance in understanding disease mechanisms and developing treatments. [1,2,3,6]