Background: Little is known of the catabolism of Lp(a). Although Lp(a) has been found to bind in vitro to numerous receptors, the relevance of these pathways has not been documented in vivo. Here, we investigated the involvement of asialo glycoprotein receptors (ASGPR) in the catabolism of Lp(a). Methods: Lp(a) was isolated from donors with various isoforms, radiolabelled and injected in native form or after desialylation into wild-type mice or ASGPR knock out mice (ASGPR + or ASGPR - mice). The catabolism from plasma and organ uptake was monitored. In addition, we investigated the metabolic fate of native Lp(a) and Lp(a) incubated for 24 h at 37 o C in human plasma in rats. Results: Native Lp(a) was catabolised faster in ASGPR + mice than in ASGPR - mice. Desialylation led to a several-fold reduction in the plasma residence time of Lp(a) and most of the asialo-Lp(a) was taken up by the liver. The Lp(a) catabolism in rats could be competitively inhibited by asialo fetoprotein (ASF), yet not by mannan. Preincubation of Lp(a) for 24 h at 37 o C significantly increased the catabolic rate of Lp(a). Conclusion: Our data suggest that the Gal-specific asialoglycoprotein receptor might be involved in the Lp(a) catabolism.