Several major University laboratories as well as Biotech Industry are conducting research on the R14del mutation in phospholamban (PLN). Phospholamban is a key regulator of the calcium cycling in heart cells, influencing heart muscle contraction and relaxation. The R14del mutation, which involves the deletion of an arginine amino acid at position 14, has been shown to disrupt the normal function of phospholamban. Laboratory investigations are using PLN-R14del animal models, cardiac cells that are derived from patient-induced pluripotent stem cells (iPSC-CMs) and in-vitro models. The studies indicate that the mutant PLN alters various pathways, including Ca-handling dysregulation, protein interactions, energy abnormalities, unfolded protein response, and protein aggregation. Each of these may contribute to disease manifestation to various degrees. Researchers aim to identify potential therapeutic strategies, such as pharmacological agents or gene therapies, to correct the dysfunctional calcium cycling caused by this mutation, aiming to prevent or mitigate the development of heart disease linked to R14del PLN.

The PLN Foundation is engaged in scientific research towards developing a treatment therapy. Over the years, we have expanded our network with (inter)national collaborations of renowned research centers. The aim is to focus research in diagnostics, treatment, and cures for heart disease caused by the Phospholamban gene mutation (PLN).

The PLN North American Foundation has the following objectives:

• Funding: Funding research for the treatment and cure of PLN heart diseases (heart rhythm problems, heart transplantation, and organ donation).
• Fellow carriers: Finding and informing individuals with the PLN mutation. We bring carriers together both online and offline to connect, share experiences, and support each other.
• Raising awareness: We aim to increase awareness leading to early treatment of the disease.