Laptm5, short for lysosomal protein transmembrane 5, is a lysosomal transmembrane protein preferentially expressed in hematopoietic cells. The human Laptm5 gene is located at position 1p34 and spans approximately 25 kb. Its protein contains five transmembrane domains, three PY motifs, and one UIM. The PY and UIM motifs can interact with various substrates, mediating protein sorting from the Golgi to the lysosome and participating in intracellular substrate transport and lysosomal stability regulation. Laptm5 is involved in processes such as autophagy activation, immunity, and inflammation regulation, and is associated with multiple diseases [1].

Conditional knockout of Laptm5 in tubules attenuates kidney fibrosis in mice with chronic kidney disease (CKD). Laptm5 contributes to tubular senescence by inhibiting WWP2-mediated ubiquitination of notch1 intracellular domain [2]. Hepatocyte-specific depletion of Laptm5 exacerbates mouse non-alcoholic steatohepatitis (NASH) symptoms, while its overexpression has the opposite effect. Laptm5 interacts with CDC42 and promotes its degradation through a lysosome-dependent manner under palmitic acid stimulation, thus inhibiting the mitogen-activated protein kinase signaling pathway [3].

In conclusion, Laptm5 plays a significant role in maintaining lysosomal function and is involved in various biological processes. The use of Laptm5 knockout or conditional knockout mouse models has revealed its importance in diseases such as CKD and NASH, providing insights into disease mechanisms and potential therapeutic targets.