USP48, also formerly known as USP31, is a member of the deubiquitinating enzymes (DUBs) family. Deubiquitination, a process it is involved in, modifies the characteristics of target proteins such as stability, intracellular localization, and enzymatic activity. USP48 is implicated in multiple biological processes and disease-related pathways, making it an important gene for functional studies [4,5].

In cancer research, gene knockout (KO) studies have revealed its significance. In a CRISPR-Cas9 screen, loss of USP48 significantly inhibited cell pyroptosis, a type of programmed cell death, by destabilizing gasdermin E (GSDME) [1]. In ovarian cancer, USP48 knockdown inhibited cell migration, invasion, and increased apoptosis after carboplatin treatment, indicating its role in chemoresistance and metastasis [3]. In colorectal cancer, blocking USP48 promoted the degradation of oncogenic HMGA2, suppressing tumor invasion and metastasis [2]. However, in another study on colorectal cancer, USP48 was found to inhibit CRC progression by stabilizing TAK1 and promoting M1-like macrophage polarization [7]. In addition, in a mouse model of bone cancer pain, spinal cord level USP48 expression was reduced, and overexpression of USP48 alleviated pain by antagonizing ubiquitin-mediated autophagic degradation of MrgC [6].

In conclusion, USP48, through its deubiquitinating function, plays diverse roles in biological processes such as pyroptosis, cell migration, invasion, apoptosis, and pain response. KO or knockdown mouse models have been crucial in uncovering its roles in diseases like cancer and bone cancer pain, providing potential therapeutic targets for these conditions.