PLEKHA6 encodes a pleckstrin homology domain-containing protein that serves multiple cellular functions through protein-protein interactions. The protein contains a WW domain that enables binding to PDZD11, facilitating the recruitment of the copper transport protein ATP7A to the cell periphery and regulation of cellular copper homeostasis 1. PLEKHA6 can form oncogenic fusion proteins, including PLEKHA6::NTRK1 fusions found in colorectal cancers with MLH1 deficiency and BRAF wild-type status 2, and PLEKHA6-NTRK3 fusions identified in Langerhans cell histiocytosis that activate MAPK signaling pathways and promote cell growth 3. The gene shows disease relevance across multiple conditions: genetic polymorphisms in PLEKHA6 are associated with psychopathology and antipsychotic treatment response in schizophrenia patients 4, while tumor expression levels correlate with breast cancer mortality, particularly showing hormone receptor status-dependent effects 5. Additionally, PLEKHA6 expression is regulated by miRNA-142 in neuronal cells and appears involved in nervous system development 6. The gene has also been identified as a potential diagnostic biomarker for osteoporosis with concurrent sarcopenia 7.