Following this primary screen, a counter-screen and a series of orthogonal experiments identified a small molecule, termed BCH-HSP-C01, that can restore the intracellular distribution of ATG9A and a second transmembrane AP-4 cargo protein, DAGLB, in neuronal models of AP-4 deficiency, including hiPSC-derived neurons from two patients with AP-4-HSP. Here, ATG9A is linked to hereditary spastic paraplegia.