In the present study, we aimed to explore TRPML1 function in lymphedema and further elucidate the effects of TRPML1 on the plasma membrane localization of AQP3 and AQP5, as well as its effect on alterations of water permeability in HLECs and the subsequent contribution to the process of lymphedema and associated inflammation. Here, MCOLN1 is linked to lymphedema.