Considerations of treatments for PK deficiency. Supportive and/or disease-targeted treatment should be considered in patients with PK deficiency with symptoms, complications, and/or impact of the disease on quality life. For symptomatic patients ≥18 years, given the reassuring safety profile and favorable clinical efficacy in a substantial subset of adults with PK deficiency, a treatment trial with a PK activator should be initiated. If effective and well-tolerated, the PK activator should be continued with ongoing monitoring. If there is no response to a PK activator, red cell transfusions could be initiated. Hematopoietic stem cell transplant (HSCT) or enrollment in a gene therapy trial could be considered in patients with significant symptoms and/or complications of anemia who are seeking a cure. HSCT outcomes may be better at a younger age. For symptomatic patients <18 years, red cell transfusions should be initiated. Enrollment in a PK activator clinical trial should be considered in those with ≥1 missense PKLR variant and significant symptoms and/or complications of anemia. If there is no response to a PK activator or a patient strongly desires a cure and has significant symptoms, HSCT or enrollment in a gene therapy trial could be considered. Patients should try a PK activator, if available, before proceeding with full splenectomy. Given the complexity of management and treatment decisions in patients with PK deficiency, consideration should be made for a discussion or referral to a hematologist with expertise in PK deficiency. Hemoglobin is indicated by Hb.