ANKRD54 (ankyrin repeat domain 54) is a nucleocytoplasmic shuttling protein that plays a critical role in regulating intracellular signaling, particularly in immune cell development and erythroid differentiation. Functionally, ANKRD54 acts as a selective modulator of Bruton's Tyrosine Kinase (BTK) nucleocytoplasmic trafficking through a specific SH3 domain-dependent interaction 1. Among human SH3 domain-containing proteins, BTK's SH3 domain is ANKRD54's prime interactor, demonstrating high specificity 2. ANKRD54 preferentially binds inactive, non-phosphorylated BTK and mediates its Crm1-dependent nuclear export, a function essential for regulating B-lymphocyte signaling 1. Beyond BTK, ANKRD54 also modulates nucleocytoplasmic shuttling of Txk/Rlk, another Tec family tyrosine kinase. Clinically, ANKRD54 expression is upregulated in elite controller-long term non-progressor (EC-LTNP) HIV-1 patients who spontaneously control viral replication, suggesting involvement in antiviral immune responses 3. The protein's role in regulating kinase subcellular localization has implications for understanding immune homeostasis and potential therapeutic targeting in immunodeficiency and infection contexts.