IDI2 (isopentenyl-diphosphate delta isomerase 2) catalyzes the 1,3-allylic rearrangement of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP), a critical step in isoprenoid biosynthesis 1. Unlike the ubiquitously expressed housekeeping isoform IDI1, IDI2 is selectively expressed in skeletal muscle and localized to peroxisomes via a PTS1-dependent pathway 2. IDI2 exhibits kinetic parameters distinct from IDI1 (Km of 22.8 μM IPP) and appears regulated independently, potentially through PPARα mechanisms 2. Recently, whole exome sequencing identified that loss-of-function IDI2 mutations eliminate exhaled isoprene in humans, establishing IDI2 as the exclusive source of DMAPP for isoprene production in skeletal muscle during lipolytic cholesterol metabolism 3. Clinically, IDI2 emerges as a potential therapeutic target for chr10 kidney disease, with proteomic integration studies identifying it among 32 validated causal proteins associated with CKD progression 4. Furthermore, IDI1 and IDI2 accumulate in Lewy bodies co-localizing with phosphorylated α-synuclein in neurodegenerative disease, suggesting roles in cholesterol metabolite production that may accelerate pathological protein aggregation 5. The lncRNA IDI2-AS1, transcribed from the IDI2 locus, regulates interleukin-5 expression and shows diagnostic potential in dilated cardiomyopathy 67.