GBA1 and Parkinson disease: Some of the proposed mechanisms linking the development of PD in association with GBA1 variants and loss of glucocerebrosidase activity include proteostatic stress secondary to misfolded GBA resulting in decreased α-synuclein degradation (2), the accumulation of lipid substrates including glucosylceramide and glucosylsphingosine which physically interact with α-synuclein (3), alterations in lysosome-mitochondrial contacts secondary to defective modulation of TCB1D15 (4), a tethering protein, and competition between misfolded GBA and other substrates for chaperone-mediated autophagy (5).