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).

Hypophosphatemic rickets, autosomal recessive, 2 is associated with 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 confirmatory for diagnosis.

No approved treatments are currently available for hypophosphatemic rickets, autosomal recessive, 2. An additional 1 compound holds orphan drug designation.

Orphan Drug Designations

While no drugs are FDA-approved specifically for hypophosphatemic rickets, autosomal recessive, 2, some of the following designated compounds may be used off-label in clinical practice. Treatment decisions should be made in consultation with a specialist familiar with this condition.

The following drugs have received orphan drug designation from the FDA for hypophosphatemic rickets, autosomal recessive, 2. Orphan designation reflects regulatory interest and does not indicate approval for treatment.

Phenotype severity distribution: 1 always present feature, 2 very common features, 1 common feature.

4 clinical trials registered. Interventions under study include drug therapy. Pipeline includes 2 PHASE3, 1 PHASE2, 1 PHASE1. Research is primarily industry-sponsored.

17 publications have been identified in PubMed for hypophosphatemic rickets, autosomal recessive, 2. Research spans Case Report / Case Series (35%), Review / Meta-Analysis (29%), and Basic Science / Preclinical (18%).

Recent Publications

• Al Qanoobi M (2026). [PMID: 41665285](https://pubmed.ncbi.nlm.nih.gov/41665285/). *J Bone Miner Res*. [Review / Meta-Analysis]

• Bruno I (2026). [PMID: 41770448](https://pubmed.ncbi.nlm.nih.gov/41770448/). *J Endocrinol Invest*. [Review / Meta-Analysis]

• Munteanu M (2026). [PMID: 41176198](https://pubmed.ncbi.nlm.nih.gov/41176198/). *Bone*. [Case Report / Case Series]

• Bertamino M (2025). [PMID: 41257790](https://pubmed.ncbi.nlm.nih.gov/41257790/). *Orphanet J Rare Dis*. [Basic Science / Preclinical]

• Ocokoljic A (2025). [PMID: 40495691](https://pubmed.ncbi.nlm.nih.gov/40495691/). *J Bone Miner Res*. [Basic Science / Preclinical]

• Srivastava S (2025). [PMID: 41251406](https://pubmed.ncbi.nlm.nih.gov/41251406/). *J Bone Miner Res*. [Basic Science / Preclinical]

• Gokul PR (2025). [PMID: 39751914](https://pubmed.ncbi.nlm.nih.gov/39751914/). *Calcif Tissue Int*. [Case Report / Case Series]

• Gokul PR (2025). [PMID: 40029431](https://pubmed.ncbi.nlm.nih.gov/40029431/). *Calcif Tissue Int*. [Other]

• Ferreira CR (2025). [PMID: 40176950](https://pubmed.ncbi.nlm.nih.gov/40176950/). *JBMR Plus*. [Case Report / Case Series]

• Collins L (2025). [PMID: 41445557](https://pubmed.ncbi.nlm.nih.gov/41445557/). *JBMR Plus*. [Case Report / Case Series]