The DDHD2 gene is highly expressed in multiple human brain regions, including the cerebellum, cortex, hippocampus, and thalamus. High levels of expression were also detected in several other human tissues; e.g. heart, brain, skeletal muscle, and testis. The DDHD2 gene has multiple transcript variants through alternative splicing. At least two transcripts were observed in humans; a major transcript of 5.4 kb and a minor transcript of 2.8 kb. The full-length protein is calculated to be 711 amino-acid long with a molecular mass of 81 kD.
DDHD2 mutations were implicated in autosomal recessive spastic paraplegia 54 (SPG54). These mutations include deletions, duplications and insertions mainly affecting the DDHD domain, which is required for the phospholipase activity. The role of the latter domain was elucidated by studies on DDHD-knockdown Drosophila model, which exhibited a reduced number of active zones at synaptic terminals. The manifestations of SPG54 in humans seem to mirror that abovementioned phenotype in Drosophila.