ANKRD44 (ankyrin repeat domain 44) functions as a regulatory subunit of protein phosphatase 6 (PP6), forming heterotrimeric complexes that regulate cellular phosphorylation events 1. The protein contains ankyrin repeat domains and associates with PP6 catalytic subunit through SAPS domain scaffold subunits, particularly PP6R1, which acts as a bridge between PP6 and ANKRD44 1. This PP6-ANKRD44 complex demonstrates specificity in cellular signaling, as knockdown of ANKRD44 enhances IκBε degradation in response to TNFα, indicating involvement in NF-κB pathway regulation 1. ANKRD44 shows disease relevance across multiple conditions. In colorectal cancer, it functions as a scaffold subunit within the PP6 complex that promotes cancer stem cell maintenance and proliferation 2. The gene exhibits methylation-driven expression changes in pancreatic cancer and shows sex-specific DNA methylation patterns in lung tissue that interact with smoking exposure 34. Additionally, ANKRD44 variants are associated with bone mineral density and lean mass through pleiotropic effects, potentially regulating PLCL1 expression 5. Clinical significance includes potential therapeutic targeting in cancer treatment, as PP6 complexes containing ANKRD44 represent druggable pathways for disrupting cancer progression and stem cell maintenance 2.