KLHL20 and its role in cell homeostasis: A new perspective and therapeutic potential

Ubiquitin ligases are proteins with the ability to trigger non-degradative signaling or proteasomal destruction by attracting substrates and facilitating ubiquitin transfer onto target proteins. Over the years, there has been a continuous discovery of new ubiquitin ligases, and Kelch-like protein 20 (KLHL20) is one of the most recent discoveries that have several biological roles which include its role in ubiquitin ligase activities. KLHL20 binds as a substrate component of ubiquitin ligase Cullin3 (Cul3). Several substrates for ubiquitin ligases (KLHL20 based) have been reported, these include Unc-51 Like Autophagy Activating Kinase 1 (ULK1), promyelocytic leukemia (PML), and Death Associated Protein Kinase 1 (DAPK1). KLHL20 shows multiple cell functions linked to several human diseases through ubiquitination of these substrates. Current literature shows that KLHL20 ubiquitin ligase regulates malignancies in humans and also suggests how important it is to develop regulating agents for tumour-suppressive KLHL20 to prevent tumourigenesis, Recent research has highlighted its potential therapeutic implications in several areas. In oncology, KLHL20's regulatory role in protein degradation pathways suggests that its targeting could offer novel strategies for cancer treatment by modulating the stability of proteins involved in tumour growth and survival. In neurodegenerative diseases, KLHL20's function in maintaining protein homeostasis positions it as a potential target for therapies aimed at managing protein aggregation and cellular stress. Here, we review the functions of KLHL20 during the carcinogenesis process, looking at its role in cancer progression, and regulation of ubiquitination events mediated by KLHL20 in human cancers, as well as its potential therapeutic interventions.