Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of purine metabolism, leading to the accumulation of 2,8-dihydroxyadenine (DHA), an insoluble metabolite that precipitates in the renal tubules and interstitium, causing crystal nephropathy. DHA crystal deposition can resemble oxalate crystals on kidney biopsy, making an accurate diagnosis challenging. Unrecognized APRT deficiency may result in irreversible kidney damage and has a high risk of recurrence after kidney transplantation. Early detection is crucial for appropriate management and preservation of kidney function. A 52-year-old woman with a history of hypertension and chronic NSAID use presented with progressive renal dysfunction, with serum creatinine rising from 1.3 mg/dL to 3.4 mg/dL over a year. Her kidney biopsy revealed interstitial inflammation, fibrosis, and crystal deposition, leading to a diagnosis of chronic interstitial nephritis. Despite treatment with corticosteroids, she progressed to end-stage kidney disease (ESKD) and underwent a living donor kidney transplantation from her 34-year-old daughter in October 2020. At 11 months post-transplant, her serum creatinine increased to 2.57 mg/dL, and an allograft biopsy revealed extensive intratubular crystal deposition without evidence of rejection or calcineurin inhibitor toxicity. Retrospective review of her native kidney biopsy suggested crystal nephropathy. Genetic testing confirmed a homozygous pathogenic variant in the APRT gene (c.294G>A, p.Trp98Ter), establishing the diagnosis of APRT deficiency. She was treated with febuxostat (40 mg/day) with significant improvement in renal function. Subsequent family screening identified asymptomatic carriers, including her kidney donor. This case highlights the challenges in diagnosing APRT deficiency, which was only identified after kidney transplantation. Delayed recognition can lead to irreversible renal damage and recurrence in the allograft. Genetic testing and APRT enzyme activity assessment should be considered in patients with unexplained crystal nephropathy to enable early intervention with xanthine oxidase inhibitors, potentially preserving renal function and preventing graft loss.