ENPP1 encodes ectonucleotide pyrophosphatase/phosphodiesterase 1 (925 aa). Nucleotide pyrophosphatase that generates diphosphate (PPi) and functions in bone mineralization and soft tissue calcification by regulating pyrophosphate levels. Highest expression in Uterus (42.3 TPM) and Thyroid (26.5 TPM).

Hypopigmentation-punctate palmoplantar keratoderma syndrome has limited evidence linking it to mutations in the ENPP1 gene on chromosome 6.

ENPP1 is classified as a druggable target (Cell Surface, Druggable Genome, and Enzyme categories) with score 0.0.

Genetic testing for ENPP1 is available. Testing is considered research-grade for diagnosis.

Phenotype severity distribution: 4 always present features, 1 common feature.

Estimated prevalence: <1 in 1,000,000 (VERY_RARE).

No clinical trials have been registered for hypopigmentation-punctate palmoplantar keratoderma syndrome.

73 publications have been identified in PubMed for hypopigmentation-punctate palmoplantar keratoderma syndrome. Research spans Case Report / Case Series (47%), Review / Meta-Analysis (32%), and Basic Science / Preclinical (11%).

Recent Publications

• Chen B (2026). [PMID: 41889596](https://pubmed.ncbi.nlm.nih.gov/41889596/). *Int Med Case Rep J*. [Case Report / Case Series]

• Cadiravane S (2026). [PMID: 41818120](https://pubmed.ncbi.nlm.nih.gov/41818120/). *J Assoc Physicians India*. [Case Report / Case Series]

• Nykaza I (2026). [PMID: 41621675](https://pubmed.ncbi.nlm.nih.gov/41621675/). *J Am Acad Dermatol*. [Review / Meta-Analysis]

• Rossel VSVJ (2026). [PMID: 41781296](https://pubmed.ncbi.nlm.nih.gov/41781296/). *J Dermatol Sci*. [Basic Science / Preclinical]

• Protonotarios I (2026). [PMID: 41936932](https://pubmed.ncbi.nlm.nih.gov/41936932/). *Hellenic J Cardiol*. [Review / Meta-Analysis]

• Alibrahim L (2026). [PMID: 41755622](https://pubmed.ncbi.nlm.nih.gov/41755622/). *Dermatol Reports*. [Gene Therapy / Novel Therapeutics]

• Nykaza I (2026). [PMID: 41621676](https://pubmed.ncbi.nlm.nih.gov/41621676/). *J Am Acad Dermatol*. [Review / Meta-Analysis]

• Assas M (2026). [PMID: 41914522](https://pubmed.ncbi.nlm.nih.gov/41914522/). *Spec Care Dentist*. [Review / Meta-Analysis]

• Piątkiewicz M (2026). [PMID: 41884385](https://pubmed.ncbi.nlm.nih.gov/41884385/). *Clin Cosmet Investig Dermatol*. [Review / Meta-Analysis]

• Almousa A (2026). [PMID: 41502835](https://pubmed.ncbi.nlm.nih.gov/41502835/). *Cureus*. [Case Report / Case Series]