s2R/TMEM97 is also involved in regulating cholesterol homeostasis by facilitating low-density lipoprotein receptor (LDLR) internalization at the plasma membrane and forming intracellular complexes in Niemann–Pick disease, type C1 (NPC1; Bartz et al., 2009; Ebrahimi-Fakhari et al., 2016; Riad et al., 2018, 2020). This evidence concerns the gene VLDLR and Niemann-Pick disease, type C1.