Hyaluronan and proteoglycan link protein 4 (HAPLN4)

Hyaluronan and proteoglycan link protein 4 (HAPLN4), also known as brain link protein 2 (BRAL2), is a member of the hyaluronan and proteoglycan link protein family that is mainly expressed in the brain, particularly in the brainstem and cerebellum[1]. HAPLN4 plays a key structural role in the formation and maintenance of perineuronal nets (PNNs)—specialized extracellular matrix structures that enwrap certain neurons and regulate synaptic stability and plasticity[1]. It interacts specifically with brevican (a brain-specific lectican), stabilizing its localization in perisynaptic spaces. This interaction is distinct from other HAPLN family members, such as HAPLN1, which associates primarily with aggrecan[1]. Genetic deletion or deficiency of HAPLN4 leads to altered PNN organization, shifts in brevican localization, and functional changes such as impaired auditory synaptic transmission and increased hearing thresholds[1]. Though not regarded as a classic pharmacological receptor, enzyme, or transporter, HAPLN4's role in matrix biology and neural function may make it of interest in research related to neurodevelopmental and neurodegenerative conditions, particularly those involving extracellular matrix dysregulation[1][3]. There are currently no drugs reported to directly target HAPLN4, nor are there established HAPLN4-specific safety concerns or approved biomarkers.

Other names

BRAL2KIAA1926Brain link protein 2Bral2hyaluronan and proteoglycan binding link protein 4