A distinct lysosome-associated sensing mechanism involves the transporter PQ Loop Repeat Containing 2 (PQLC2) and the Chromosome 9 Open Reading Frame 72 – Smith-Magenis Syndrome Chromosomal Region Candidate Gene 8 – WD Repeat Domain 41 (C9orf72–SMCR8–WDR41/CSW) protein complex, which is recruited to the lysosomal membrane during amino acid starvation. This evidence concerns the gene SLC66A1 and Smith-Magenis syndrome.