TTC28 (tetratricopeptide repeat domain 28) is a conserved vertebrate protein with essential roles in chr22 stability and cell division. Primary Function: TTC28 regulates mitosis and cytokinesis, potentially involved in spindle midzone microtubule condensation during midbody formation 1. Mechanism: TTC28 functions as a substrate of chaperone-mediated autophagy (CMA), interacting with HSPA8 through its tetratricopeptide repeat domains to bind the C-terminal PTIEEVD motif in HSPA8 1. This CMA-mediated degradation serves as a master regulator of TTC28's ability to maintain genome stability 2. TTC28 knockout cells exhibit three-fold higher micronuclei frequency (7.7% vs 2.3%, P=4.86E-09) compared to wild-type cells, indicating compromised chr22 stability 1. Disease Relevance: TTC28 is frequently mutated and downregulated in numerous human cancers 1. L1 retrotransposon-mediated transductions originating within TTC28 occur in 34% of endometroid ovarian cancers and 31% of clear cell ovarian cancers 3. Clinical Significance: Elevated TTC28 expression correlates with improved genomic stability, suggesting therapeutic potential for cancer prevention. Additionally, TTC28 has been identified as a potential therapeutic target in meningioma (OR=2.03; 95% CI=1.60-2.57) 4.