TRPA1 is a lysosomal Ca2+ release channel in DRG neurons. Several TRP channels are localized at both plasma membranes and intracellular membranes, such as ER, secretory vesicles, endosomes, and lysosomes. The compositions of lipids (PI(3,5)P2 for lysosomes and PI(4,5)P2 for the plasma membrane) and luminal ions are indicated for each compartment. In the DRG neurons, TRPA1 has a dual location: plasma membrane (PI(4,5)P2 enriched) and lysosomes. Upon activation by TRPA1 agonists such as AITC, plasma membrane TRPA1 mediates Ca2+ influx and lysosomal TRPA1 mediates Ca2+ release from lysosomes ([Ca2+]lumen is ∼0.5 mM) at the periphery of the cell near plasma membrane. Ca2+ release through TRPA1 activation is sufficient to activate Ca2+ sensors (e.g., synaptotagmins) in the VAMP2-localized DCVs, triggering DCV exocytosis and neuropeptide (CGRP and NPY) release. TRPMLs are present on all lysosomes (pH 4.6; [Ca2+]lumen is ∼0.5 mM Ca2+; PI(3,5)P2), mediating Ca2+-dependent lysosomal exocytosis, membrane trafficking, and transport through Ca2+ sensors (calcineurin/ALG-2/CaM/synaptotagmins). In the cytoplasm, the ER may provide Ca2+ to lysosomes through ER–lysosome membrane contact sites.