The human ether-a-go-go (hERG) gene encodes the Kv11. 1 cardiac K+-channel involved in ventricular repolarization. Loss of hERG functional plasma membrane (PM) expression is associated with long-QT syndrome type-2 (LQT2), characterized by increased risk of cardiac arrhythmia and sudden cardiac death. Many LQT2 associated mutations induce conformational defects in the hERG channel that result in recognition and degradation by distinct protein quality control machinery operating at the endoplasmic reticulum (ER) and at post-Golgi (peripheral) compartments, including the PM. Several established hERG ‘pharmacochaperones’ can partially reverse the mutant conformational defect and promote hERG trafficking by binding to a site within the channel pore. However, functional restoration of hERG current is precluded because pharmacochaperone binding causes hERG channel block. Using cell-based biochemical screens, we identified two novel small-molecule rescuers of hERG channel functional expression, designated as D8 and A29. Unlike previously-described pore-blocking pharmacochaperones, D8 and A29 neither block the hERG channel nor otherwise alter its function. These compounds do not alter the partially compromised ER conformational maturation efficiency of the hERG mutants, containing missense mutations in their PAS domain. Instead, they act selectively at post-Golgi compartments by inhibiting the rapid endocytosis and lysosomal delivery of a broad range of mutant and drug acquired processing defective misfolded hERG channels. These compounds potentially represent a new class of drug which enhance hERG functional expression without concurrent channel blockade. In addition, the ability of these drugs to influence hERG cellular processing at post-Golgi compartments but not the ER adds to the growing appreciation for peripheral quality control systems; both as an important mechanism in conformational disease pathogenesis and as a potential therapeutic target.