STAMBPL1, also known as STAM binding protein-like 1, is a Lys-63 linkage-specific deubiquitinase [2]. It is involved in multiple biological pathways. For example, it functions in concert with E3 ubiquitin ligase RNF167 to control the polyubiquitination level of Sestrin2 in response to leucine availability, which in turn modulates mTORC1 signaling [1]. It also participates in pathways related to the stability of proteins like EGFR, AXL, and MKP-1, as well as in the regulation of RNA splicing [2,4,5].

Knockout of STAMBPL1 in a human colon cancer cell line suppresses xenograft tumor growth, suggesting its role in promoting cancer progression [1]. In hepatocellular carcinoma, STAMBPL1 deficiency attenuates liver tumorigenesis both in vitro and in vivo [2]. In lung adenocarcinoma, knockdown of STAMBPL1 in A549 and H1299 cells suppresses cell growth, migration, invasiveness, and colony-forming ability while increasing apoptosis [3]. In breast cancer, depletion of STAMBPL1 sensitizes cells to cisplatin both in vitro and in vivo [5]. In gastric cancer, knockdown of STAMBPL1 significantly suppresses cell proliferation, increases apoptosis, and decreases invasion and migration [6].

In conclusion, STAMBPL1 plays crucial roles in multiple biological processes mainly through its deubiquitinase function. Studies using knockout models in various cancer cell lines have revealed its significant contribution to cancer progression in colon, liver, lung, breast, and gastric cancers, highlighting its potential as a therapeutic target in these disease areas.