Below we review the underlying mechanisms of LQTS subtypes centering the attention on the trafficking-deficient variants identified in each case:Loss-of-function KCNQ1 variants linked to LQTS1 can be classified according to their pathophysiological mechanisms: variants can disturb ion permeation, gating, trafficking, Kv7.1-KCNE1 interaction, PKA-mediated signaling, phosphatidylinositol biphosphate binding, and calmodulin binding140–142. Here, KCNE1 is linked to familial long QT syndrome.