Lysosomal BK Channels as an Emerging Therapeutic Target for Lysosomal Dysfunction

Lysosomes are acidic organelles that serve as the primary degradative compartments and critical signaling hubs within the cell. Dysregulation of lysosomal function is implicated in a spectrum of human diseases, many of which lack effective therapies. Central to lysosomal activity is the maintenance of ion homeostasis and membrane potential, which are governed by an array of transporters and ion channels. Among the lysosomal ion channels identified to date, potassium channels, especially the large-conductance calcium-activated potassium (BK) channel and TMEM175, have recently garnered significant interest. The lysosomal BK channel, which is characterized by high sensitivity to intracellular calcium and voltage, is emerging as a crucial component in positive feedback regulatory loops. Despite the pivotal role of the lysosomal BK channel, therapeutic targeting of the lysosomal BK channel remains a largely unexplored frontier. This review comprehensively examines the current understanding of the structure and function of lysosomal BK channels and discusses emerging strategies for targeting these channels to develop novel treatments for lysosomal dysfunction-related diseases.