CRISPR-Cas9 ribonuclear particles were programmed with gRNAs designed to create inactivating indels in 23 LSD genes implicated in sphingolipidoses (GBA1, ASAH1, HEXA, HEXB, PSAP, SMPD1), NCL (CLN1, CLN2, CLN3, DNAJC5, CLN5, CLN6, CLN7, CLN8, ATP13A2, GRN, CTSD, CTSF), LSD gene products that reside in the lysosomal membrane (MCOLN1 (encoding TRMPL1), NPC1, NPC2), as well as LIPA (Wolman’s disease) and GAA (Pompe’s disease) and then transfected into parental H9NGN2;TMEM192-HA cells (referred to hereafter as Control cells) (Extended Data Fig. 3a; Supplementary Table 3). Here, CTSD is linked to sphingolipidosis.