GID8 is a core component of the CTLH E3 ubiquitin ligase complex that plays multiple regulatory roles in cellular signaling and metabolism 1. As part of the CTLH complex, GID8 selectively accepts ubiquitin from UBE2H and mediates ubiquitination and proteasomal degradation of specific substrates 1. A critical function of GID8 is serving as a positive regulator of Wnt signaling by promoting nuclear accumulation and retention of β-catenin 2. Upon Wnt activation, GID8 translocates to the nucleus where it binds and retains β-catenin, facilitating Wnt-stimulated gene expression 2. GID8 also regulates glutamine metabolism by controlling the expression of glutamine transporters (SLC1A3) and glutaminase (GLS), thereby modulating cellular metabolic demands 3. The protein demonstrates significant clinical relevance in colorectal cancer, where nuclear GID8 is upregulated and correlates with β-catenin nuclear accumulation and poor prognosis 2. Additionally, GID8 expression is regulated by YTHDF1 in an m6A-dependent manner, with high GID8 expression associated with aggressive tumor progression 3. The CTLH complex containing GID8 also modulates host anti-microbial responses and has been implicated in neurodegenerative diseases, where it interacts with phosphorylated tau proteins 45.