HSD17B10 encodes a multifunctional mitochondrial protein with dual roles in metabolic and RNA processing functions. Primarily, HSD17B10 catalyzes 17-beta-hydroxysteroid dehydrogenase activity and participates in isoleucine and steroid metabolism 1. Beyond its dehydrogenase function, HSD17B10 moonlights as a non-catalytic component of mitochondrial ribonuclease P (mtRNase P), essential for tRNA 5'-end cleavage 2. As part of the MRPP1-MRPP2 subcomplex, HSD17B10 facilitates tRNA maturation by catalyzing N1-methylguanine and N1-methyladenine formation at position 9 in tRNAs and enhancing 3'-end processing efficiency 3. Lysine succinylation at position K99 maintains mtRNase P stability and HSD17B10's interaction with binding partners 3. Pathogenic HSD17B10 variants cause HSD10 mitochondrial disease, an X-linked disorder presenting across severity spectrum from neonatal to atypical forms 4. Neonatal presentations feature metabolic acidosis, hyperlactatemia, hepatic dysfunction, cardiomyopathy, and early death 5, while infantile-onset disease shows progressive neurodegeneration, retinopathy, and cardiomyopathy from 6-18 months 4. The pathogenic mechanism appears independent of dehydrogenase function but relates to compromised mtRNase P activity and subsequent mitochondrial dysfunction. HSD17B10 knockdown impairs metabolic homeostasis and elevates oxygen consumption 6. No effective treatment currently exists for HSD10 disease.