Background & Objective: The lysosome is a membrane-enclosed organelle widely found in
every eukaryotic cell. It has been deemed as the stomach of the cells. Recent studies revealed that it
also functions as an intracellular calcium store and is a platform for nutrient-dependent signal transduction.
Similar with the plasma membrane, the lysosome membrane is furnished with various proteins,
including pumps, ion channels and transporters. So far, two types of lysosomal potassium channels
have been identified: large-conductance and Ca2+-activated potassium channel (BK) and
TMEM175. TMEM175 has been linked to several neurodegeneration diseases, such as the Alzheimer
and Parkinson disease. Recent studies showed that TMEM175 is a lysosomal potassium channel with
novel architecture and plays important roles in setting the lysosomal membrane potential and maintaining
pH stability. TMEM175 deficiency leads to compromised lysosomal function, which might be
responsible for the pathogenesis of related diseases. BK is a well-known potassium channel for its
function on the plasma membrane. Studies from two independent groups revealed that functional BK
channels are also expressed on the lysosomal plasma membrane. Dysfunction of BK causes impaired
lysosomal calcium signaling and abnormal lipid accumulation, a featured phenotype of most lysosomal
storage diseases (LSDs). Boosting BK activity could rescue the lipid accumulation in several LSD
cell models. Overall, the lysosomal potassium channels are essential for the lysosome physiological
function, including lysosomal calcium signaling and autophagy. The dysfunction of lysosomal potassium
channels is related to some neurodegeneration disorders.
Conclusion: Therefore, lysosomal potassium channels are suggested as potential targets for the intervention
of lysosomal disorders.