Mutations in the ATP13A2 gene are associated with various neurodegenerative diseases, including Kufor-Rakeb syndrome (KRS), hereditary spastic paraplegia type 78 (SPG78), neuronal ceroid lipofuscinosis type 12 (CLN12), and amyotrophic lateral sclerosis (ALS). This study reports a case of a rare homozygous mutation in the ATP13A2 gene (Exon12 c.1062G>T: p.Lys354Asn). The patient, a 35-year-old female, initially presented with involuntary tremors in both upper limbs, which were considered posture- and action-induced myoclonus. The symptoms progressively involved both lower limbs, accompanied by bradykinesia, spastic gait in the lower limbs, cognitive impairment, and psychiatric behavioral abnormalities. Electromyography (EMG) revealed paroxysmal EMG discharges in both lower limbs when the patient was in the standing and semi-recumbent positions, with irregular discharge frequencies. Somatosensory evoked potential testing indicated a significant increase in P25 amplitude, suggesting a cortical origin of the myoclonus. The patient was treated with levetiracetam combined with clonazepam to alleviate the myoclonus and levodopa/benserazide combined with pramipexole for parkinsonian symptoms. Significant improvements were observed in myoclonus, muscle rigidity, and bradykinesia, and the patient regained independent ambulation. This mutation site in this patient has not been previously reported in the PubMed database, the Chinese Medical Journal (CMJ) Full-Text Database, Wanfang Database, or the China National Knowledge Infrastructure (CNKI). Amino acid conservation analysis indicated that this site was highly conserved among six vertebrate species, including humans, rats, mice, cattle, chimpanzees, and pigs. According to the genetic mutation classification standards and guidelines of the American College of Medical Genetics and Genomics (ACMGG), this mutation is considered likely pathogenic, exhibiting overlapping phenotypic features of KRS and SPG78. The phenotype of coarse limb myoclonus of cortical origin represents the first reported case associated with this gene, thereby expanding its clinical phenotypic spectrum.