RNF170 (ring finger protein 170) functions as an E3 ubiquitin-protein ligase that plays essential roles in protein degradation and cellular regulation. The protein mediates ubiquitination-dependent degradation of inositol 1,4,5-trisphosphate receptor type 1 (ITPR1) through the endoplasmic reticulum-associated degradation (ERAD) pathway 1. RNF170 interacts with ERLIN1/2 scaffolds on the ER membrane, which bridge its interaction with TMUB1 and regulate cholesterol transport and secretory pathway function 2. The protein also promotes K48-linked polyubiquitination and degradation of various targets, including DEK protein, which regulates the RIPK1-PANoptosis pathway in inflammatory responses 3. Structural studies reveal RNF170 forms flexible complexes with Erlin proteins, though the exact binding mechanism remains unclear 4. Clinically, RNF170 mutations cause distinct neurological disorders: heterozygous mutations lead to autosomal dominant sensory ataxia with age-dependent gait abnormalities and reduced proprioception 15, while biallelic loss-of-function mutations cause autosomal recessive hereditary spastic paraplegia with progressive lower limb spasticity 67. These phenotypes likely result from disrupted ITPR1 regulation and altered cellular calcium signaling in neurons.