Degradation of endoplasmic reticulum (ER) by selective autophagy (ER‐phagy) is crucial for ER homeostasis. However, it remains unclear how ER scission is regulated for subsequent autophagosomal sequestration and lysosomal degradation. Here, we show that oligomerization of ER‐phagy receptor FAM134B (also referred to as reticulophagy regulator 1 or RETREG1) through its reticulon‐homology domain is required for membrane fragmentation in vitro and ER‐phagy in vivo. Under ER‐stress conditions, activated CAMK2B phosphorylates the reticulon‐homology domain of FAM134B, which enhances FAM134B oligomerization and activity in membrane fragmentation to accommodate high demand for ER‐phagy. Unexpectedly, FAM134B G216R, a variant derived from a type II hereditary sensory and autonomic neuropathy (HSAN) patient, exhibits gain‐of‐function defects, such as hyperactive self‐association and membrane scission, which results in excessive ER‐phagy and sensory neuron death. Therefore, this study reveals a mechanism of ER membrane fragmentation in ER‐phagy, along with a signaling pathway in regulating ER turnover, and suggests a potential implication of excessive selective autophagy in human diseases. Synopsis How endoplasmic reticulum (ER) membranes are fragmented for subsequent autophagic degradation (ER‐phagy) is ill‐defined. CAMK2B‐dependent phosphorylation of ER‐phagy receptor FAM134B promotes its oligomerization and membrane scission activity, a process deregulated in sensory neuropathy. ER‐phagy receptor FAM134B oligomerizes through its reticulon‐homology domain (RHD). FAM134B oligomerization is required for ER membrane scission prior to autophagosomal engulfment. ER stress triggers the activation of CAMK2B, which phosphorylates FAM134B to enhance ER membrane fragmentation and ER‐phagy. An HSAN type‐II patient‐derived variant, FAM134B‐G216R, forms higher‐order oligomers and induces massive ER‐phagy, which leads to sensory neuron death. CAMK2B‐dependent phosphorylation of autophagy receptor FAM134B promotes its oligomerization and membrane‐scission activity, a process deregulated in sensory neuropathy.