Rtn4ip1, also known as optic atrophy-10 (OPA10), is a mitochondrial NAD(P)H oxidoreductase. It plays a crucial role in coenzyme Q (CoQ) biosynthesis by regulating the O-methylation activity of COQ3, which is essential for mitochondrial respiration activity in muscle tissue [1]. Additionally, it may be involved in processes related to amino acid transport as well as having implications in cell cycle regulation, drug resistance, and metastasis based on bioinformatics analysis [2,3].

In Rtn4ip1-knockout myoblasts, CoQ9 levels were markedly decreased and cellular respiration was impaired [1]. Muscle-specific knockdown of dRtn4ip1 in flies led to impaired muscle function, which could be reversed by dietary CoQ supplementation [1]. In esophageal squamous cell carcinoma (ESCC), depletion of RTN4IP1 impaired cell proliferation, induced apoptosis, abrogated amino acid uptake, and down-regulated amino acid transporters, highlighting its role in ESCC carcinogenesis [2]. In breast cancer, high expression of RTN4IP1 was associated with a poor prognosis [3]. In thyroid cancer, knockdown of RTN4IP1 increased cellular proliferation, invasion, migration, colony formation, and tumor spheroid formation, suggesting a tumor-suppressive function [6]. In optic neuropathy and rod-cone dystrophy, biallelic variants in RTN4IP1 have been identified as causative factors [4,5,7,8,9,10].

In conclusion, Rtn4ip1 is essential for mitochondrial respiration through its role in CoQ synthesis. Studies using gene knockout and knockdown models in various organisms have revealed its significance in multiple disease areas, including muscle-related disorders, different types of cancers, and optic neuropathies with or without associated retinal dystrophies. These models have provided valuable insights into the biological functions of Rtn4ip1 and its potential as a therapeutic target in these diseases.