STAMBPL1, also known as STAM binding protein-like 1, is a Lys-63 linkage-specific deubiquitinase [2]. It is involved in multiple cellular pathways and has significant biological importance. It plays roles in regulating protein stability, RNA splicing, and various signaling pathways such as mTOR, Wnt/β -catenin, and NF-κB, which are crucial for normal cell function, metabolism, and are often dysregulated in diseases [1,5,6,7]. Genetic models, like knockout models, are valuable for studying its functions.

Knockout of STAMBPL1 or correction of its heterozygous mutation in a human colon cancer cell line suppresses xenograft tumor growth, indicating its role in promoting cancer progression in colorectal tumors [1]. In hepatocellular carcinoma, STAMBPL1 deficiency attenuates liver tumorigenesis in vitro and in vivo. It removes K63-linked ubiquitin chains from EGFR to avoid lysosome degradation and activates cleavage of the K63-linked ubiquitin chain on TOE1 to enhance RNA efficient splicing of EGFR [2]. In lung adenocarcinoma, knockdown of STAMBPL1 in A549 and H1299 cells suppresses cell growth, migration, invasion, and colony-forming ability, while increasing apoptosis [3]. In kidney renal clear cell carcinoma, silencing STAMBPL1 can decrease the mesenchymal phenotype and enhance the anti-tumor efficacy of cancer therapy [4]. In gastric cancer, STAMBPL1 knockdown significantly suppresses cell proliferation, increases apoptosis, and decreases invasion and migration of AGS cells [6].

In conclusion, STAMBPL1 is a key deubiquitinase involved in multiple cellular processes. Model-based research, especially knockout studies, has revealed its crucial role in promoting tumorigenesis in various cancers, including colorectal, liver, lung, kidney, and gastric cancers. Understanding STAMBPL1 functions provides potential therapeutic targets for these cancer types.