Recently, biallelic variants in HPDL (4‐hydroxyphenylpyruvate dioxygenase‐like) were identified as causes of a rare mitochondrial encephalopathy (ME), associated with a broad range of clinical manifestations, from severe, infantile‐onset neurodegeneration to pure or complex spastic paraplegia. Here, HPDL is linked to Mitochondrial encephalopathy.