CRISPR/Cas9 genome-wide screens using sterol-sensitive endogenous HMG-CoA reductase (HMGCR) reporter identify the sterol-responsive RNF145 and gp78 as independently responsible for sterol-accelerated degradation of HMGCR, the rate-limiting enzyme of cholesterol biosynthesis.
Impaired GABAergic and glutamatergic synaptic function and loss of interneurons in the amygdala, hippocampus, and cerebellum cause characteristic disease symptoms in a mouse model juvenile neuronal ceroid lipofuscinosis.
A new family of sterol-specific lipid transfer proteins has been found that anchors in the endoplasmic reticulum; some of these proteins stretch across membrane contacts and mediate sterol traffic from the plasma membrane.
The dual role of Drosophila Mitofusin in steroid hormone production and cholesterol ester storage, which is evolutionary conserved by the combined expression of the two mammalian Mitofusins, ensures proper synaptic development.
Genetic analysis of a CLN4 Drosophila model suggests that the disease-causing alleles act as dominant gain of function mutations that cause CSPα oligomerization and impair secretory and prelysosomal trafficking.